Metronidazole is a substrate and possibly a weak inhibitor of CYP3A4. It is an inhibitor of CYP2C9. There are no data indicating mechanism-based inhibition of CYP3A4 or CYP2C9, and it is not listed as an inducer of CYP enzymes.

Metyl-5- nitroimidazol ethanol. M=171. Slightly soluble in water. Cyclic tertiary amine.

Metronidazole is indicated for the treatment of infections caused by Trichomonas vaginalis. Reported side effects that can be confused with an acute porphyria attack are nausea, vomiting, diarrhoea and abdominal pain. Dark-colouring of urine may take place.

Metronidazole is a substrate of CYP3A4 (Wang 2000). 30-60% is metabolised mainly in the liver via oxidation and 60-80% is excreted as unchanged drug. The elimination half-life is 6-10 hours. Metronidazole is listed as a weak CYP3A4 inhibitor (Cheng 2010, Obach 2006) and in vitro studies have shown that it is unlikely to be a perpetrator in drug-drug interactions (Polasek 2011, Sinz 2006). There are no data indicating mechanism-based inhibition. A case study showed that ciclosporin, a CYP3A4 substrate, increased in plasma concentration when co-administered with metronidazole (Herzig 1999). Other in vivo data have on the other hand, showed that metronidazole is not an inhibitor of CYP3A4 (Blyden 1988, Wang 2000). It is listed as a weak inhibitor of CYP2C9 (Holsetin 2012, Isoherranen 2009, Mouly 2009). There are conflicting in vivo data on whether metronidazole inhibits CYP2C9 or not when co-administrated with phenytoin. It has been observed that metronidazole increased the area under the curve and the half-life elimination, and decreased the clearance of phenytoin (Blyden 1988), but another study showed that metronidazole did not affect the pharmacokinetics of phenytoin (Jensen 1985). Other in vivo data have shown that there was a statistically significant increase in INR (Laine 2000) and in drug plasma concentration in patients, when warfarin was co-administered with metronidazole (O’Reilly 1976). Warfarin is a substrate of CYP2C9 and these data indicates that metronidazole can inhibit CYP2C9. There are however, no data indicating mechanism-based inhibition.

Thunell: 2 patient reports of tolerance.

Systemic use: uneventful use reported in 6 patients with acute porphyria (1 report for suppository, G01A F01. 5 reports for infusion, J01X D01). Topical use: uneventful use reported in 3 patients with acute porphyria (cream, D06B X01).